Phosphorus oxychloride → Benzyl 3-Formylindole-2-carboxylate

HRID 982028Notes

Reaction equation

HRID 982028 reaction equation
P(Cl)(Cl)(Cl)=O.CN([CH:14]=[O:15])C1C=CC=CC=1.[NH:16]1[C:24]2[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=2)[CH:18]=[C:17]1[C:25]([O:27][CH2:28][C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)=[O:26].O.C([O-])(=O)C.[Na+]>ClCCCl.O>[CH:14]([C:18]1[C:19]2[C:24](=[CH:23][CH:22]=[CH:21][CH:20]=2)[NH:16][C:17]=1[C:25]([O:27][CH2:28][C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)=[O:26])=[O:15]

Participants

7

Reactant 4

HCID 24813Phosphorus oxychlorideHCID 66737N-MethylformanilideHCID 7723355benzyl 1H-indole-2-carboxylateHCID 23681166Acetic acid, sodium salt, monohydrate

Product 1

HCID 14583464Benzyl 3-Formylindole-2-carboxylateYield 80.3%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 962WaterSolvent

Procedure

A mixture of 6.5 ml (70 mmol) of phosphorus oxychloride and 9.3 ml (70 mmol) of N-methylformanilide was stirred at ambient temperature. The resulting mixture was diluted with 90 ml of 1,2-dichloroethane, treated with 15.0 g (59.8 mmol) of benzyl indole-2-carboxylate, and heated at reflux for 1 h. After being allowed to cool for 5 min, the warm solution was poured into an ice-cold solution of 60 g of sodium acetate hydrate in 200 ml of water. The resulting mixture was stirred for 1 h, filtered, and the yellow solid was washed twice with water and twice with ether, and air-dried. The filtrate was treated with 400 ml of hexane and filtered. The combined solids were digested with hot ethyl acetate, cooled to 0° C., and filtered to give 13.41 g (80%) of the desired compound as an off-white solid. 1H NMR (CDCl3 /CD3OD) δ 5.50 (s,2H), 7.3-7.55 (m, 8H), 8.38 (d,J=9 Hz,1H). Mass spectrum: (M+H)+ =280.

Workup

  1. temperatureheated
  2. temperatureat reflux for 1 h
  3. temperatureto cool for 5 min
  4. stirringThe resulting mixture was stirred for 1 h
  5. filtrationfiltered
  6. washthe yellow solid was washed twice with water and twice with ether
  7. customair-dried
  8. additionThe filtrate was treated with 400 ml of hexane
  9. filtrationfiltered
  10. temperaturecooled to 0° C.
  11. filtrationfiltered

Sources & evidence

ORD record
ord-1a1dea1bf6a14f3e8b7127447387af93
Source dataset
uspto-grants-1991_02
Patent number
US04994477

Reaction notes

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